Lack of a quantitative assay precludes investigation of human liver regeneration. A potentially useful assay in vitro will be evaluated in rats. The rate of incorporation of thymidine triphosphate into deoxyribosenucleic acid (DNA) by isolated liver nuclei will be compared with the rate of DNA synthesis in vivo at several intervals after removal of various amounts of liver. If DNA synthesis in vitro correlates with results obtained in vivo, the intensity and time course of human liver regeneration following hepatic resection for trauma or tumor will be studied by the isolated nuclei technique. Inhibition of hepatic regeneration by exogenous glucagon in eviscerated dogs suggests that cyclic adenosine monophosphate (cyclic AMP) may influence replication of DNA in mammalian liver. The hypothesis will be studied in whole animals and in isolated nuclei. The rate of DNA synthesis after partial hepatectomy will be investigated in rats pharmacologically treated to raise intracellular levels of cyclic AMP. The effect of exogenous cyclic AMP on DNA syntheis in vitro by nuclei isolated from regenerating liver will be measured. Alteration of DNA synthesis in either system would suggest that cyclic AMP may be a factor in the intracellular regulation of hepatic regeneration.